Osteosarcoma Seminar, September 2011

Speaker Dr. Matthew Pead, BVetMed PhD MRCVS FHEA CertSAO Senior lecturer in orthopaedics, Royal Veterinary College. Introduction to forms of cancer;Dr. Pead started the seminar with some fundamental terminology, which he used a variety of fruits and sheets of plastic to clearly illustrate. The words cancer, neoplasia and tumour mean essentially the same thing and are often interchangeable terms. Two further terms we often hear are benign and malignant. A benign tumour generally refers to an enclosed or encapsulated growth that has well defined margins separating the diseased growth from the healthy tissue that surrounds it, making it relatively easy to remove surgically. It does not interact with the surrounding tissue other than by pushing it aside. It does not invade surrounding tissues directly, but retains its distinct margins. In the case of benign tumours in the bone, they can cause issues by stimulating the bone to reshape itself around the growth, which can weaken or distort the bone to such a degree that it becomes brittle and malformed. A malignant tumour is an invasive growth which extrudes itself into the surrounding tissue as it spreads, rendering it very difficult to determine where the healthy tissue ends and the diseased tissue starts. Furthermore, it can be metastatic, meaning that it releases tiny seed-like microscopic metastasis into the body, which themselves take root and grow into secondary cancers at various points around the body. There are of course various types of malignant tumours and osteosarcoma is a particularly aggressive form. Osteosarcoma is a tumour originating from within the bone, which is malignant, metastatic and very aggressive. 95% will metastasize and invade the lungs, giving rise to new cancerous growths there, called secondary tumours. It has also been known to generate new primary tumours in the bone at other sites across the body, such as in a second limb. This extreme malignancy –or tendency to invade and spread at great speed- is what makes osteosarcoma among the most difficult cancers to treat. Progression of the illness.Osteosarcoma usually starts with a dog presenting mild lameness in one limb, very often in the end of one of the long bones, but can be found in any part of the skeleton. The common veterinary response is to treat for soft tissue injury, such as a sprain, with an anti-inflammatory drug and perhaps something to reduce the pain, and then rest the dog for a week or so. Usually the lameness continues, sometimes getting worse and the dog is generally returned to the vet and they will then most likely take an x-ray, especially in the case of large or giant breeds. This is when most osteosarcoma is confirmed. Because there is such a distinctly characteristic appearance to osteosarcoma, x-ray is 90% accurate for diagnosis, but for absolute certainty, a biopsy should also be taken. If there are visible secondary tumours seen in further x-rays of the lungs at this stage, it means that treatment options are essentially no longer available, the illness has already gone too far to make anything but palliative care or euthanasia viable. If there are no secondary tumours seen in a lung x-ray, it does not mean that they are not there, only that they are likely to still be microscopic. It does however mean that certain other radical approaches might be considered to prolong the dog’s life for a few extra months. From the dog’s point of view, all it knows is that it is in pain and that this pain steadily increases. It is of paramount importance for the owner to remember this- this is a very painful cancer and the pain is progressive. Therefore, pain reduction is a major concern in treatment choices. Causes and affectsOsteosarcoma is a cancer more commonly found in large and giant breed dogs and the assumption is that the mechanism that causes their increased growth also makes them more vulnerable to developing osteosarcoma. It is a cancer that can be found in all breeds, but in general it is found most commonly in the long bones of the giant breeds, whereas it may be found in any bone in small and mid-sized breeds. Unlike with human cases, it is not a condition that emerges during adolescence, but can occur throughout the dog’s life. It is not known how long an early potential osteosarcoma may have been present in the bone before it becomes active and starts its very aggressive progression, however once it starts, this tends to be very fast. It is also not known if previous bone injuries give rise to a susceptibility to develop osteosarcoma but this is thought to be unlikely based on comparative studies on cases with and without previous bone injuries. It is also possible for this form of cancer to invade virtually any other tissue type as well as utilising the lymphatic system to spread. What characterises osteosarcoma the most is that you essentially get rapid bone creation and bone destruction in the same area. It is not the only process that does this, but it is the most likely to do so. Panosteitis appears to involve the calcium metabolism of the growing puppy, and over-supplementing calcium in puppy diets can increase the incident of pano, however there is no known link with osteosarcoma development. X-ray evidence and diagnosisDr. Pead then showed us a series of examples of x-rays images to help illustrate the illness and its progression, from very early to late stage tumours. In perhaps the starkest image, a dog that was known to have normal knee formation four weeks previously, (having undergone cruciate ligament repair), was shown with a stifle joint literally exploded with an invasive osteosarcoma tumour spreading into the surrounding tissue- all of which change occurred in just the four weeks. The fast, aggressive progression of this cancer cannot be over stated. He also showed examples of metastases visible in the lung of an affected dog. But again, it is worth pointing out that if a chest x-ray in a confirmed osteosarcoma case does not yet show visible secondary tumours in the lungs, it does not mean that they are not yet there. It simply means that they have probably not yet grown big enough to see. Treatment options1-Removal of the primary tumourThis can be very difficult to achieve due to the invasive nature of the cancer and the need to take clear margins around it. Obviously, on a long limb bone it is not generally possible at all. It invades surrounding tissue so much, that in the vast percentage of cases, you are actually facing total limb amputation anyway. There is no way to treat the tumour other than surgical removal, nothing kills the cancer. Fortunately, chemotherapy drugs do appear to be somewhat affective with slowing the secondary metastasises, but will not have any influence on the primary osteosarcoma. 2- Amputation,Radical though it at first seems, this option removes pain, removes the primary cancer, and removes a large amount of excess weight rather than forcing the dog to haul it around. It is not a small operation, but it is relatively straight forward and uncomplicated providing that the remaining limb is strong and healthy. Most dogs cope remarkably well on three legs, even a large breed such as a Leonberger, especially if it is a hind leg removed as they carry more weight on their front legs. This option leads to an average 8 to 14 months survival rate. The dog must also have chemotherapy however, or secondaries will progress to a terminal state in 4 months or less. The same applies to limb salvage 8- 14 months with chemo, 4 months without. 3-Limb salvageThere are a range of techniques being offered, some of them still quite new and costs can be very high. As with complete amputation, salvaging the limb with either a metal prosthesis, the insertion of bone grafts or through the use of other techniques will not address the secondary growths and owners must assume that their dogs will have further cancers spreading in the lungs etc. Complex implants and reconstructions can also lead to further complications because of the extensive wounds and fragile state of the bone left behind. Having said that, most canine patients recover very well from even major surgery, so long as they receive appropriate pain medication. Survival time post limb salvage is essentially the same as it is for amputation, 8 to 14 months, provided chemotherapy is also used.4- ChemotherapyUsually 4 to 6 cycles of chemotherapy (especially platinum based varieties) will likely be administered, which dogs tolerate fairly well, avoiding many of the unpleasant side effects that afflict many human chemo patients. This will commonly be used along side either limb salvage or amputation. But it only delays, it does not cure. This is because it is virtually impossible to eliminate all of the microscopic metastatic cells, which have properties much like stem cells, meaning that they are very potent in their ability to be mobile, to take root and to grow aggressively. Chemotherapy alone (without amputation or limb salvage procedures), will in very general terms add about 4 months to a dog’s life. If a dog is also being medicated for a pre-existing auto-immune issue, this can lead to complications with chemotherapy as the two classes of medications can have issues when combined. 5- Palliative therapy - Pain relief.In advanced osteosarcoma, morphine alone will have little impact on relieving the pain being experienced. Radiotherapy can temporarily reduce the pain, as will a class of drugs called bisphosphonates, which slow the progression of bone remodelling and therefore the pain associated with it. This will only ever be a temporary treatment strategy. Owners can assume 2 months survival with pain relief alone. But even the strongest pain relief will have a limited effect. The pain will be there, it will progress, and it will impact on the quality of the dog’s life. This is an agonising illness. 6-Euthenasia.Every owner must ask themselves what the impact of any form of medical intervention will be on the quality of life that their dog experiences. The distress, the confusion and the incessant pain will become worse and worse with time. That is the sad truth of this illness. Further research Dr. Pead touched on recent efforts to explore the possibility of vaccinations against cancers such as sarcomas, but this is apparently producing no tangible results so far. Similarly, there is no proven link between conventional vaccinations and osteosarcoma rates. Also, as far as he is aware, there is no body of data examining rate of growth and rates of osteosarcoma in later life. This would be an excellent project for a body such as the Leonberger Club to take on. He stated that hard evidence for familial predisposition of osteosarcoma is quite weak at present and as yet there is no research group that has identified a likely candidate gene for the condition. However Dr. Pead felt quite strongly that genetics would ultimately prove to be the key, saying. “Every breed specific disease that has been scientifically investigated, where you can show that its breed related, has genetics at the bottom of it”. He touched on several examples of ongoing studies and the short falls associated with many of them, (as well as the danger of surfing the internet for solutions). There were questions raised about whether diet had a role to play, for which he said there is no hard evidenceThe likelihood is that this is a polygenic characteristic, therefore the only solution is to do population statistics. The solution is to breed away from the main population trends, i.e. a great many of the problems that we see in pedigree dogs are the result of a “squeezed gene pool”, therefore seek diversity. There was a prolonged and very informative Q&A which is best appreciated through viewing the entire DVD, rather than trying to condense into this summary. There is undoubtedly a need for further research and he was quick to support recent efforts of the LCGB to encourage owners to participate in the Broad Institute / AHT osteosarcoma study. This will be a slow process though and so he cautioned us to not expect a solution to this illness anytime soon. Osteosarcoma Research Collaboration.The UK’s Animal Health Trust is collaborating with researchers at the Broad Institute in the United States in a study looking at the genetic basis of osteosarcoma in a number of pedigree dog breeds. The Leonberger is now one of their target breeds. The AHT has invited Leo owners to submit DNA samples through the use of cheek swab kits which will be available through the LCGB health committee, or directly from the AHT.These kits are simple to use, with clear instructions and can be done at home. The researchers are particularly keen to get samples from three types of Leos; 1- those who unfortunately may have already been diagnosed with this form of cancer; 2- those with close relatives who had the illness; 3- And finally, Leos over the age of 7 who are healthy and clear of any signs of cancer. If your dog unfortunately has a suspected osteosarcoma please ask your vet to place a small piece (a 3-5mm cube) of the biopsy of the suspected tumour (normally removed for diagnostic histopathology) in a special preservative (‘RNAlater’) provided by the AHT upon request, (see contact details below).Osteosarcoma is probably the most common form of cancer our breed suffers from. This is a rare opportunity for we, as a breed community, to do our part in helping scientists learn more about this awful illness. The cheek swab kits and full instructions, along with prepared envelopes for return of samples, can be obtained by contacting any member of the LCGB health subcommittee or by contacting Dr. Mike Starkey (Tel: 01638 555603; E-mail: mike.starkey@aht.org.uk).Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK.